tbuckley/cabot-search huggingface dataset:
Durvalumab outcomes for patients with PD-L1 positive and negative stage III unresectable non-small cell lung cancer treated at veterans health administration facilities.
Authors: Elizabeth M. Burton, Amanda Moore, Zohra Nooruddin, Ion Cotarla, Daniel Simmons, Laura Davis, Kelly R Reveles, Paromita Datta, Gabriel Roman Souza, Omoruyi Credit Irabor, Kathleen Franklin, Xavier Jones, Christopher R Frei
Journal: Journal of Clinical Oncology (2023)

e18793 Background: Clinical trials and real-world studies have documented the benefit of durvalumab consolidation therapy in patients with stage III unresectable non-small cell lung cancer (UR-NSCLC) following chemoradiotherapy (CRT). Methods: Patients with stage III UR-NSCLC on durvalumab following CRT, at any Veterans Health Administration (VHA) facility from 1/1/17 to 6/30/20, were included. Patients were followed from their durvalumab initiation date through the earliest of their last VHA visit, loss to follow up, death, or end of study. Electronic health record and chart review data were retrospectively collected to determine baseline characteristics, number of durvalumab doses, length of follow-up, and overall survival (OS). Chi-square and Wilcoxon rank sum tests were used to compare baseline characteristics for patients with PD-L1 negative (&lt;1%) and positive (1% or greater) tumors. Kaplan-Meier curves were constructed for OS. Cox proportional hazards regression, with controls for divergent baseline characteristics, were used to compare OS between the two groups. Results: Of 935 available patients, 340 had PD-L1 results: 221 had PD-L1 positive (65%) and 119 had PD-L1 negative (35%) tumors. The two groups of patients were largely similar with respect to baseline characteristics, including age, sex at birth, White race, smoking status, marital status, Charlson Comorbidity Index, ECOG status, histology, stage, EGFR, and RAS mutations (Table). Patients with PD-L1 positive and negative tumors had a similar median (interquartile range [IQR]) number of durvalumab doses (15 [6-24] vs 12 [5-23], p=0.38) and length of follow-up (31.5 [12.1-43.5] vs 28.7 [12.2-40.6] months, p=0.43). Kaplan-Meier survival curves were similar for patients with PD-L1 positive and negative tumors: estimated 12-month OS rates (95% CI) of 84% (78%-88%) vs 89% (81%-93%) and 24-month OS rates of 72% (65%-78%) vs 76% (67%-84%); median OS was not reached in patients with PD-L1 positive tumors and was 47.0 months for the PD-L1 negative group. Cox Proportional Hazards regression analysis also demonstrated similar OS for both groups (p=0.64). Conclusions: In this real-world study of a subpopulation of VHA patients with stage III UR-NSCLC and known PD-L1 levels, survival benefits with durvalumab were consistent with those reported in the PACIFIC trial, despite having worse baseline prognostic factors. Patients with PD-L1 positive and negative tumors experienced similar overall survival, including 12- and 24-month OS rates.[Table: see text]
Impact of pregnancy in women with desmoid fibromatosis: An international retrospective observational study.
Authors: Marco Fiore, Sylvie Bonvalot, Giulia Personeni, Chandrajit P Raut, Kelly Mercier, Rebecca Gladdy, Silva Ljevar, Dimitrios Tzanis, Enrica Rossi, Megan Sulciner, Harini Suraweera, Chiara Colombo, Mikhael Rabih, Marianna Coppola, Catherine Sarre-Lazcano, Sara Iadecola, Costanza Figura, Daniela Salvatore, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2023)

11513 Background: Desmoid fibromatosis (DF) often occurs during pregnancy/peripartum. Guidance for planning new pregnancies during active surveillance or following DF resection has been limited. Thus, we sought to evaluate outcomes and decision making in the peripartum. Methods: Women of child-bearing age with DF diagnosed between 2000 and 2020 were interviewed about procreation decisions, in a multicenter retrospective observational study (NCT05284305). Pregnancies simultaneous or after diagnosis were analyzed. Primary outcome was DF progression/recurrence within 1 yr postpartum. Secondary outcomes were spontaneous regression, switch to active treatment, and obstetric risks. To estimate probability of progression, a random intercept logistic model was fit to account for correlation of progression in multiple pregnancies in the same patient. Results: Of 483 pts interviewed, 120 (24.8%) postponed, 32 (6.6%) interrupted, and/or 232 (48%) avoided pregnancy (in 93.3%, 50%, and 72.9% of cases because of DF), respectively. 147 pregnancies in 131 pts were concurrent with or after diagnosis: 26 (17.7%, Group A) concurrent with diagnosis, 48 (32.7%, B) after DF resection, and 73 (49.7%, C) with DF on surveillance. Estimated probability of progression was 12.0% (CI 2.0 – 48.4) during pregnancy and 15.8% (5.6 – 37.5) postpartum; for pregnancies after diagnosis (Groups B and C), these rates were 5.1% (0.4 – 40.0) and 9.0% (1.8 – 35.0). On multivariate analysis, age at pregnancy and size of primary DF were significant risk factors for progression (Table). Estimated probability of spontaneous regression was 3.6% (CI 0.2-40.7) during pregnancy and 7.1% (CI 0.3 – 67.2) postpartum. 7/38 (18.4%) spontaneously regressed after pregnancy-related PD, 4/23 (17.4%) in Groups B and C. Treatment for progression was needed in 9/79 (11.4%) postpartum, in 4/63 (6.3%) in Groups B and C. Obstetric complications were comparable to population data in developed countries. Conclusions: After DF diagnosis, pregnancy is safe with a risk of progression of 5% during pregnancy and 9% postpartum. Treatment is needed in only 6%. Spontaneous regression is less common but occurs even after initial progression. Patients decision making about procreation appeared to be influenced by their DF diagnosis. This study supports counseling that fertility options should be fully explored with expert guidance as intervention rates are low. [Table: see text]
Multi-omics analysis to reveal the change of peripheral blood TCR repertoire and tumor burden during neoadjuvant chemotherapy combined with sequential PD-1 blockade for patients with non-small cell lung cancers: A single-center, single-arm phase 2 trial.
Authors: Bo Yang, Chaoyang Liang, Qi Song, Qi Xiong, Jie Li, Yaping Long, Wenhao Zhou
Journal: Journal of Clinical Oncology (2023)

e20582 Background: Preoperative neoadjuvant chemotherapy combined with immunotherapy has been applied to the treatment of non-small cell lung cancer (NSCLC). However, the optimal dosage of chemotherapy and sequencing for chemotherapy and immunotherapy remains controversial. Methods: In this single-arm phase 2 trial, patients with stage IB to IIIA resectable NSCLC were enrolled and received 2 cycles of dose-limiting platinum-based chemotherapy (albumin-bound paclitaxel or pemetrexed plus cisplatin or carboplatin) on day 1, combined with sintilimab (200mg) on day 5 before undergoing radical surgery. Combination postoperative adjuvant therapy with the same regimen was administered. The primary endpoints were objective response rate (ORR) and major pathological response (MPR). Biopsies and plasma at different timepoint were collected and performed with RNA sequencing, circulating tumor DNA sequencing and T cell receptor (TCR) sequencing. Results: 17 patients were enrolled. After neoadjuvant treatment, patients with completed response, partial responses and stable diseases were 11.8% (2/17), 70.6% (12/17) and 17.6% (3/17), respectively, yielding an ORR of 82.4%. Radiological downstaging was achieved in 82.4% (14/17) of patients. All patients (17/17, 100%) experienced the R0 resection. Pathologic complete response and MPR were identified in 35.2% (6/17) patients and 23.5% (4/17) patients, respectively. Only 1 of the 17 patients (5.9%) experienced grade 3 or greater adverse event. Multi-omics analysis revealed chemotherapy combined with sequential PD-1 blockade results in the increase of dominated TCR clones and the decrease of the tumor burden. Especially during chemotherapy of cycle 1, the dominated TCR clones were significantly increased, and the maxVAF of ctDNA was significantly decreased. The change between the dominated TCR clones and maxVAF of ctDNA was negatively correlated. Conclusions: In patients with stage IB to IIIA resectable NSCLC, the neoadjuvant therapy with dose-limiting platinum-based chemotherapy combined with sequential sintilimab was safer and resulted in significant antitumor activity in patients with resectable NSCLC. The changes in TCR repertoire and ctDNA during treatment were analyzed, which provided evidence for the rationality of neoadjuvant chemotherapy combined with sequential PD-1 blockade. Clinical trial information: ChiCTR2000033092 .
Uptake of MRI in patients without a personal history of breast cancer (PHBC) classified as “high risk”.
Authors: Luciarita Boccuzzi, Shirlene Paul, Chelsea McPeek, Lisa Stempel, Rosalinda Alvarado, Mia Alyce Levy
Journal: Journal of Clinical Oncology (2023)

e18754 Background: The American Cancer Society (ACS) recommends annual screening MRI in addition to mammography in patients without a personal history of breast cancer (PHBC) who are ages 25-75 with a Tyrer-Cuzick (TC) score ≥ 20%. Here, we evaluate the uptake of supplemental MRI in these high-risk patients. Methods: Data was extracted from the EMR of an academic medical center for patients (ages 25-75) with a mammogram between 07/20/2020 and 07/19/2021 and a TC ≥ 20%. We assessed uptake differences in demographics, access to healthcare, and breast density in the patient populations that opted for supplemental MRI. A chi-squared analysis was used to compare the groups: 1) No supplemental screening, 2) Patients who underwent MRI supplemental screening, and 3) Patients who did not receive MRI supplemental screening. Results: Of the 1144 patients with a TC ≥ 20%, 27% (n = 307) underwent supplemental MRI screening, while 73% (n = 837) did not. Out of 635 patients with an MRI order, those who were recommended by a high-risk breast cancer (HRBC) provider (n = 227, 36%) were more likely to undergo the MRI (88%, n = 200) compared to those without a HRBC provider (33%, n = 135) (p-value &lt; 0.001). However, the other 509 patients that were recommended MRI never followed up for further imaging or health care visits. Of the patients who were notified that they had dense breasts (n = 842, 74%), 28% (n = 237) underwent MRI, compared to those without dense breasts (18%, n = 55) (p-value &lt; 0.001). Conclusions: 27% (n = 307 out of 1144) of women without a PHBC who are at high-risk for breast cancer underwent MRI as a supplemental breast cancer screening. Our study shows that access to a HRBC is a contributing factor to follow through with the recommended MRI as a supplemental screening. More than 80% of the patients who underwent MRI had a HRBC. Patients may still be faced with challenges, including having access to a HRBC.
COVID-19 vaccination, infection, and symptoms among cancer survivors in the United States during 2021.
Authors: Nova Yang, Xuesong Han, Robin Yabroff, Jingxuan Zhao, Zhiyuan Zheng
Journal: Journal of Clinical Oncology (2023)

e18786 Background: The effects of the COVID-19 pandemic on cancer survivorship during 2021, the second year in the US when vaccination became widely available, is largely undocumented. This study reports COVID-19 vaccination, infection, and symptoms among cancer survivors using nationally representative data. Methods: We used the 2021 National Health Interview Survey to identify adults with and without cancer history. Age-adjusted percentages for COVID-19 vaccinations, infection history and symptom severity were calculated among adults with and without a cancer history. We further calculated the percentage of COVID-related outcomes stratifying by sex, age, race/ethnicity, education level, and health insurance coverage among cancer survivors. Results: Compared to adults without a cancer history (n = 26,023), cancer survivors (n = 3,428) were more likely to have two or more COVID-19 vaccines (66.6% v 62.3%, P= 0.003) and as likely to have COVID-19 infection history (14.1% vs 14.2%, P= 0.93), but once infected, face higher likelihood of developing moderate/severe symptoms (62.5% v 54.2%, P= 0.02). Among cancer survivors, older age, higher educational attainment, and having health insurance coverage were significantly associated with higher vaccination rate (all P&lt; 0.001). Age was significantly associated with COVID-19 infection history, with the highest percentage of COVID-19 infection history (17.3%) among cancer survivors aged 45-54 years. Among cancer survivors infected with COVID-19, being female and younger age were associated with higher likelihood of developing moderate to severe symptoms (both P&lt; 0.05). Moreover, loss of taste or smell were most frequently seen among COVID-19 infected cancer survivors who were female (68.7%), 45-54 years of age (71.1%), Hispanic (73.2%), and survivors younger than 65 years without private insurance (75.1% for publicly insured and 73.1% for uninsured). Conclusions: In 2021, cancer survivors had better COVID-19 vaccine completion than adults without a cancer history. If infected, cancer survivors were more likely to develop moderate/severe symptoms; survivors who were female, younger age, Hispanic or uninsured had worse experiences with COVID-19 infection, suggesting ongoing tailored efforts to prevent infection are warranted as the pandemic evolves.
Results from phase I/II study of NY-ESO-1-specific TCR gene-transduced T cell therapy (TBI-1301, mipetresgene autoleucel) in patients with advanced synovial sarcoma.
Authors: Akira Kawai, Mikiya Ishihara, Tomoki Nakamura, Shigehisa Kitano, Shintaro Iwata, Kohichi Takada, Makoto Emori, Koji Kato, Makoto Endo, Yoshihiro Matsumoto, Shigeki Kakunaga, Eiichi Sato, Yoshihiro Miyahara, Kunihiko Morino, Shinya Tanaka, Shuichi Takahashi, Akihiko Matsumine, Shinichi Kageyama, Takafumi Ueda
Journal: Journal of Clinical Oncology (2023)

11558 Background: Synovial sarcoma is one of malignant soft tissue tumors with a poor prognosis. A cancer-testis antigen NY-ESO-1 is expressed in the tumors of 50-80% synovial sarcoma patients. The purpose of this study was to evaluate the safety and the efficacy of gene engineered autologous T cell product with NY-ESO-1 siTCR retroviral vector which expressed affinity-enhanced NY-ESO-1-specific TCR and siRNA to silence endogenous TCR (TBI-1301). Methods: This was an open label phase I/II study to evaluate safety, appearance of replication competent retrovirus (RCR), appearance of clonality, in vivo cell kinetics and clinical responses. TBI-1301 were manufactured from each subject’s leucocytes stimulated with anti-CD3 antibody and Retronectin and transduced with NY-ESO-1 siTCR retroviral vector. TBI-1301 was infused at split dose of 5 x 10 9 cells following cyclophosphamide treatment at 750 mg/m 2 for two days to HLA-A*02:01 or HLA-A*02:06 positive subjects with synovial sarcoma expressing NY-ESO-1, which were surgically unresectable and refractory to anthracycline therapy. Results: Eight subjects were enrolled and treated with TBI-1301. The objective response rate was 50.0% with best overall partial response in 4 of 8 subjects according to RECIST v1.1/irRECIST and the median overall survival was 650 days. Cytokine release syndrome (CRS) occurred in 50.0% (4/8) and consisted of 1 subject with grade 1 CRS and 3 subjects with grade 2 CRS. All subjects who developed CRS recovered with prespecified treatment, in which 2 subjects were treated with symptomatic therapy, 1 subject was treated with tocilizumab and 1 subject was treated with both tocilizumab and corticosteroid. No subjects had immune effector cell- associated neurotoxicity syndrome (ICANS). RCR and clonal dominance were not detected in any subjects throughout the study period. Conclusions: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumors will become a promising treatment for advanced or recurrent synovial sarcoma with acceptable toxicity. Clinical trial information: NCT03250325 .
Robotic CT guided biopsy to aid histological confirmation of recurrent lymphoma in cases where tissue sample is challenging to obtain through conventional percutaneous methods.
Authors: Prashant Bamania, Elliot Elwood, Thomas Millard, Sam Smith, Nasir Khan, Nicos Fotiadis, David Cunningham, Ed Johnston, Bhupinder Sharma
Journal: Journal of Clinical Oncology (2023)

e18796 Background: Histological confirmation of recurrent lymphoma, suspected on clinical history or imaging, enables the determination of an optimal treatment regimen. Conventional percutaneous biopsy methods often involve computed tomography to plan ‘freehand’ needle paths that will often require multiple in procedure adjustments which increases the risk of collateral damage. In cases where suspected recurrent disease is challenging to access using conventional methods, such as lesions close to major structures or located within the retroperitoneum, histological diagnosis can be delayed. Robotic CT guided biopsy allows precise lesion targeting, minimizing the risk of collateral injury, enabling minimally invasive tissue diagnosis in difficult to access lymphoproliferative disease. The aims of this analysis were to assess the safety of robot assisted biopsy by analyzing the related complications and the effectiveness of robotic CT guided biopsy via the sufficiency of histological specimens obtained. Methods: Retrospective consecutive analysis of 11 patients who underwent robotic CT guided biopsy between the months of January and October 2022 in the context of suspected recurrent lymphoproliferative disease. The decision for robotic guided biopsy was based on a multidisciplinary team assessment of the radiology and proposed target sites. Tissue sample adequacy and histological diagnosis were recorded from local histopathology reports. Biopsy related complications were recorded within a 4-month follow-up period from clinical documentation. Results: 11 patients underwent robotic CT guided biopsy. Sufficient samples consisting of at least 2 cores were obtained in all patients. 9 patients were identified with a recurrent form of lymphoma. 1 patient was negative for recurrence. In 1 case an insufficient sample was obtained. No biopsy related immediate or late complications were recorded. Conclusions: We find that, with careful case selection, robotic CT guided biopsy is allowing us to safely obtain a histological diagnosis in suspected recurrent lymphoma where conventional methods are deemed challenging. In the single case where an insufficient sample was obtained significant patient agitation was documented, highlighting that a static target remains of importance with robotic CT guided biopsy. The targeting accuracy the technique provides is allowing optimal treatment planning in a higher proportion of cases.
BRCA mutations in triple negative breast cancer patients in Guatemala: A descriptive study.
Authors: Alba Kihn-Alarcón, Diana Beatriz Marroquin Flores, Vicky de Falla, Mauricio Siliézar, Carlos Silva, Angel Velarde
Journal: Journal of Clinical Oncology (2023)

e22543 Background: In Guatemala, breast cancer is the most common malignancy among women, the habitants in the country are characterized by being of different ethnic groups and little is understood about the prevalence of germline mutations and their influence in the prognosis and diagnosis of triple negative breast cancer patients, reason why the aim of our study is to determine the prevalence of BRCA1 and BRCA2 germline mutations among this population. Methods: Forty-five patients with confirmed biopsy of triple negative breast cancer by immunohistochemistry treated at Liga Nacional Contra el Cáncer-INCAN Guatemala in 2022 were enrolled in the study. Triple negativity was defined as &lt; 1% estrogen, progesterone and HER2 staining by immunohistochemistry or not amplified by fluorescence in situ hybridization in those with HER2 borderline result. After consent, patients had next generation sequencing and multiplex ligation-dependent probe amplification for BRCA1 and BRCA2 genes. From medical records, we obtained: demographic, clinico-pathological and treatment data. Median was calculated for age, while frequencies and percentages were computed for the categorical variables. Results: The study identified 19 patients with a BRCA1 or BRCA2 germline mutations (42.22%). The median age at cancer diagnosis was 39 vs. 49 years old compared to patients with lack of mutations of the genes analyzed. The majority harboring a mutation (36.84%) were from the countryside, especially the regions IV and V (southeast and central). Among all groups, (66.67%) were diagnosed with locally advanced disease and initially treated with neoadjuvant chemotherapy. According to our findings, the most prevalent mutations were located in the BRCA1 gene (47.37%), with BRCA1 c.212+1G &gt; A and BRCA2 c.2806_2809del being the most frequent variants (36.84%). Conclusions: Triple negative breast cancer patients in Guatemala have higher prevalence of BRCA1 and BRCA2 mutations than reported among other populations, longer follow up of this study is expected to confirm the results and further understand how the presence of mutations could affect the response to treatment of the patients, their prognosis and the impact in their families. [Table: see text]
Pretreatment radiomic biomarker for immunotherapy responder prediction in IB-IV stage NSCLC: A multi-center retrospective study.
Authors: Shaowei Wu, HaiYu Zhou, Daipeng Xie, Lintong Yao
Journal: Journal of Clinical Oncology (2023)

e21060 Background: The current biomarker of immune checkpoint inhibitors (ICIs) efficacy is not sufficient. This study investigated the correlation between radiomic biomarker and immunotherapy responder in patients with IB-IV stage non-small-cell lung cancer (NSCLC), including its biological explanation for ICIs treatment response prediction. Methods: CT images from 319 pretreatment NSCLC patients receiving immunotherapy between January, 2015 and November, 2021 were retrospectively collected and were distributed into a discovery (n = 214), independent validation (n = 54), and external test cohort (n = 51). 851 features were extracted from both tumoral and each peri-tumoral VOIs. The reference standard is the durable clinical benefit (DCB) and the crucial exclusion criteria are missing pretreatment CT scans. The predictive value of combined radiomic signature (CRS) was assessed in a cohort of 98 resectable NSCLC patients receiving ICIs. The association of radiomic features and tumor immune landscape on the online dataset (n = 60) was also evaluated. A clinical model was constructed and incorporated with radiomic signature to improve performance further. Results: CRS discriminated between DCB and non-DCB patients in the training cohort (area under the curve (AUC): 0.82, 95% CI: 0.75 to 0.88)) and independent cohort (AUC: 0.75, 95%CI: 0.62 to 0.88). In this study, the predictive value of CRS was better than PD-L1 expression (AUC of PD-L1 subset: 0.59, 95%CI: 0.50 to 0.69) or clinical model (AUC of validation cohort: 0.66, 95%CI: 0.51 to 0.81). When predicting pathological response, CRS divided patients into a major pathological response (MPR) and non-MPR group (AUC: 0.76, 95%CI: 0.67 to 0.81). Moreover, CRS showed a promising stratified ability on overall survival (OS; HR: 0.48, 95%CI: 0.27 to 0.89; p = 0.020) and progression-free survival (PFS; HR: 0.43, 95%CI: 0.26 to 0.74; p = 0.002). Biological pathway analysis on online dataset revealed that dysregulation of Hedgehog and Hippo signaling pathways got involved in the prediction of radiomic features. Conclusions: By analyzing both tumoral and peri-tumoral regions of CT images in a radiomic strategy, we developed a non-invasive biomarker distinguishing responder from ICIs therapy, which might inform clinical decisions on the use of ICIs in advanced as well as resectable NSCLC patients.